Researchers have identified two genetic variants that increase the risk of women developing endometriosis.
The genomes of 5,500 women with the condition from the UK, US and Australia were compared to those of 10,000 healthy volunteers.
The Nature Genetics study could lead to more effective treatments and diagnosis, researchers said.
An endometriosis charity said more research was needed to show how this could lead to better treatments.
Researchers from the University of Oxford, the Queensland Institute of Medical Research in Australia and Harvard Medical School, Boston were all involved in the study.
They say their findings provide clues to why endometriosis occurs.
They identified chromosome 1 and chromosome 7 as being crucial to a women's risk of developing the condition.
Chromosome 7 is thought to be involved in regulating genes which develop the womb and its lining, the study says, while chromosome 1 is close to a gene which is important for hormone metabolism and the development of the female reproductive tract.
Dr Krina Zondervan, lead author of the study and research fellow at the University of Oxford, said: "Our study is a breakthrough because it provides the first strong evidence that variations in DNA make some women more likely to develop endometriosis," says Dr Krina.
"We now need to understand the effect of these variations on cells and molecules in the body."
Endometriosis is a common gynaecological disease which affects around six to 10% of all women in their reproductive years.
Common symptoms include chronic pelvic pain, painful periods as well as serious fertility problems in some women.
The condition occurs when cells like those in the lining of the womb are found elsewhere in the body.
During a woman's monthly cycle, hormones stimulate the endometriosis, causing it to grow, then break down and bleed.
This leads to inflammation, pain, and the formation of scar tissue (adhesions).
The only way to diagnose endometriosis is through a procedure called a laparoscopy which happens under general anaesthetic.
Current treatments are limited to surgery and hormonal drugs which can have side effects.
Dr Stephen Kennedy, senior author of the study and head of the Nuffield department of obstetrics and gynaecology at Oxford, said this could now change.
"We have great confidence that the results of this study will help towards developing less invasive methods of diagnosis and more effective treatments for endometriosis."
Helen North, from Endometriosis UK, welcomed the study.
"However, what we really need is to see how this discovery can lead towards effective treatments.
"It takes around 10 years for a women to be diagnosed and even then available treatments are few, not definitive, and can involve invasive surgeries."